The fibrotic pneumoconioses are an important group of occupational lung diseases induced by the inhalation of toxic particulates. The pathogenesis of these lung diseases is not well understood. Silicosis, one such fibrotic pneumoconiosis, is induced by the inhalation of Alpha-quartz particles. The immune and pathogenetic mechanisms of silicosis have partially characterized in other laboratories using such animal models as the rabbit, rat, hamster, guinea pig and monkey. Whereas past emphasis has centered on the effect of silica administration on the immune system, my research objective focuses on the effect of the immune system on the host's response to silica. To accomplish this objective, a murine model of experimental silicosis has been developed in this laboratory and proven especially well suited for exploring the following research areas (1) the role of T lymphocytes including T helper and T suppressor cell populations in the initiation and perpetuation of silica-induced pulmonary inflammation and (2) the relationship between the effects of T cell deficiency and any resulting deviations in pulmonary inflammation and silica-induced collagen deposition and collagen metabolism. These goals will be accomplished using a mouse model of experimental silicosis developed in this laboratory by the intratracheal instillation of silica crystals. Pulmonary inflammation will be quantitated in mice deficient in T cells or deficient in just T helper or T suppressor cell populations in order to implicate a possible role for these cells in the pathogenesis of silica-induced damage. In-depth studies will determine if T cells play a role in silica-induced cellular influx or accumulation, in the influx into the lungs of a specific cell type, in silica-induced proteinosis in the pulmonary milieu and in modulating the activity of enzymes in the lungs that have the potential for tissue damage. Another manifestation of silica-induced pathogenesis is the deposition of collagen within the lung parenchyma. The role of T cells including T helper and T suppressor cell populations in the amount of collagen deposited, in alterations in collagen-type ratios and in changes in collagen synthesis rates will be evaluated in the murine model of experimental silicosis. Both acute and chronic stages of silica-induced inflammation and fibrosis will be examined in fulfillment of these two objectives.